ABSTRACT
Although mesenchymal stem cell-derived exosomes (MSC-exos) have been shown to have therapeutic effects in experimental periodontitis, their drawbacks, such as low yield and limited efficacy, have hampered their clinical application. These drawbacks can be largely reduced by replacing the traditional 2D culture system with a 3D system. However, the potential function of MSC-exos produced by 3D culture (3D-exos) in periodontitis remains elusive. This study showed that compared with MSC-exos generated via 2D culture (2D-exos), 3D-exos showed enhanced anti-inflammatory effects in a ligature-induced model of periodontitis by restoring the reactive T helper 17 (Th17) cell/Treg balance in inflamed periodontal tissues. Mechanistically, 3D-exos exhibited greater enrichment of miR-1246, which can suppress the expression of Nfat5, a key factor that mediates Th17 cell polarization in a sequence-dependent manner. Furthermore, we found that recovery of the Th17 cell/Treg balance in the inflamed periodontium by the local injection of 3D-exos attenuated experimental colitis. Our study not only showed that by restoring the Th17 cell/Treg balance through the miR-1246/Nfat5 axis, the 3D culture system improved the function of MSC-exos in the treatment of periodontitis, but also it provided a basis for treating inflammatory bowel disease (IBD) by restoring immune responses in the inflamed periodontium.
Subject(s)
Humans , Colitis , Exosomes , Periodontitis/therapy , Periodontium , T-Lymphocytes, Regulatory , Th17 CellsABSTRACT
<p><b>OBJECTIVE</b>To explore the molecular basis for an individual with CisAB subtype of the ABO blood group.</p><p><b>METHODS</b>ABO antigen and serum antibody of the proband were detected with a serological method. Exons 5 to 7 of the ABO gene were amplified with PCR and sequenced bidirectionally. Allele-specific amplification for exon 6 to 7 was also carried out.</p><p><b>RESULTS</b>The proband was assigned as a CisAB phenotype based on his serological characteristics. Heterozygous variations including 220C/T, 261G/del, 297A/G, 467C/T, 646A/T, 681A/G, 771C/T, 803G/C, 829A/G and 1009A/G of the ABO gene were identified through direct sequencing, which was assigned as CisAB01var/O02 genotype. Allele-specific amplification indicated that the proband carried an O02 allele and a CisAB01var allele. Compared with A102, the CisAB01var allele has two nucleotide substitutions at 803G>C and 1009A>G, which resulted in replacement of amino acid Gly by Ala at position 268 and Arg by Gly at position 337.</p><p><b>CONCLUSION</b>The CisAB subtype was identified with 803G>C and 1009A>G variants in the α1,3-N-acetyl-galactosaminyltransferase gene compared with that of the A102 allele.</p>
ABSTRACT
There is no a systemic performance metrics for clinical data management. While the CDMC in China starts to develop the quality metrics for clinical data management, it is essential to think over the performance and pursue metrics implementation of clinical data management in China. This article provides the basic concept, development and implementation of the performance metric in clinical data management.
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Case report form (CRF) is a key document for data collection in clinical trials. A well-designed CRF is required for database construction, data accuracy, data query/cleaning, CRF completion and statistical analysis. A well-defined process or SOP should be in place for CRF design. Data collection should fully meet the demand of study protocol. The layout of CRF should be clear with well-structured fields and standard coding for fields.
ABSTRACT
Establishment of quality management system (QMS) plays a critical role in the clinical data management (CDM). The objectives of CDM are to ensure the quality and integrity of the trial data. Thus, every stage or element that may impact the quality outcomes of clinical studies should be in the controlled manner, which is referred to the full life cycle of CDM associated with the data collection, handling and statistical analysis of trial data. Based on the QMS, this paper provides consensus on how to develop a compliant clinical data management plan (CDMP). According to the essential requirements of the CDM, the CDMP should encompass each process of data collection, data capture and cleaning, medical coding, data verification and reconciliation, database monitoring and management, external data transmission and integration, data documentation and data quality assurance and so on. Creating and following up data management plan in each designed data management steps, dynamically record systems used, actions taken, parties involved will build and confirm regulated data management processes, standard operational procedures and effective quality metrics in all data management activities. CDMP is one of most important data management documents that is the solid foundation for clinical data quality.
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Objective To analyze the diagnosis and therapy of pemphigus and pemphigoid.Methods Clinical data were retrospectively analysed for 648 patients with pemphigus or pemphigoid admitted in Huashan Hospital,Fudan University from 2003 to 2007.Results The mean age of onset of pemphigus was younger than that of pemphigoid(47.0±16.9 years vs 65.1±13.9 years.P＜0.001).Of 175 patients with pemphigus confirmed by direct immunoflorescence(DIF),100%were positive for IgG,and 92.0%for C3,while out of 223 patients with pemphigoid,51.12%were positive for IgG,99.1%for C3.For pemphigus,the consistency reached 68.8%among clinical diagnosis.pathological diagnosis and immunological(DIF)diagnosis,80.7%between pathological and immunological diagnosis.In the case of pemphigoid,the consistency was 62.8%among clinical,pathological and immunological diagnosis,and 78.1%between pathological and immunological diagnosis.Corticosteroids were primary treatment strategy for both pemphigus and pemphigoid.and prednisone of 0.5-1.5 mg per kilogram bodyweight per day could control the condition of most patients.Conclusions DIF could be used as an important diagnostic means for patients with pemphigus or pemphigoid which can not be confirmed by clinical manifestation or pathology.In primary hospitals,IgG and C3 are recommended for DIF testing when pemphigus is suspected,and C3 is recommended for suspected pemphigoid.
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Objective To investigate the association between HLA classⅡgenes and bullous pem-phigoid(BP).Methods HLA-DRB1,DQA1,DQB1were determined by polymerase chain reaction se-quence specific oligonucleotide probe methods in56patients with BP and150normal controls from Shanghai area.Results It was shown that HLA-DRB1*10(*1001)was linked to DQB1*0501,and its frequency in-creased significantly in BP group compared to normal controls.There was a positive correlation between DRB1*1001and mucosal involvememt as well as autoantigen BP230.HLA-DRB1*04was linked to DQB1*0302,and its frequency increased significantly in BP group compared with normal control.There was a positive correlaton between DRB1*04and autoantigen BP180.The frequency of HLA-DRB1*12(*1201,*1202)decreased in BP group compared to normal controls.Conclusions It is suggested that HLA-DRB1*1001and DRB1*04be the susceptible genes while DRB1*1201,and*1202be the protective genes of BP patients in Shanghai area.
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Objective To investigate hepatitis B virus mutation rate after the universal immunization in China. Methods DNA sequence analysis of the “a” determinant was performed on sera from 72 viral carrier children after immunoprophylaxis selected through a sampling survery. Results Four mutants were detected, the mutation rate was 5.56%. One strain showed Gly-to-Arg mutation at the 145 codon of surface antigen. Animo acid substitutions at the amino acid 126 and 140 were noted in the other three children. The epidemiological HBV serotype shifted from previous adw infection to more recent adr was also observed. Conclusions These observations indicate that vaccination is probably the cause of mutation, whereas the mutation is low and it will certainly not be a reason for doubting that the vaccination is the method of main choice for preventing hepatitis B infection that still devastates the developing countries.
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Objective To probe the Th cytokine pattern in pemphigus,so as to clarify the pathogenesis of pemphigus and draw up new therapy.Methods Reverse transcription-polymerase chain reaction(RT-PCR)was used to examine the interferon gamma(IFN-?)and interleukin10(IL-10)mRNA expression on peripheral blood mononuclear cells(PBMCs)of20cases of pemphigus in acute stage,20cases in stable stage,and20normal controls.Results The IFN-?mRNA expression in20cases of pemphigus in acute stage was higher than that of controls(P